Conventionally, mental disorders are divided into types based on criteria sets with defining features. DSM-IV (American Psychiatric Association, (1993-ISBN 0-89042-061-0)) is the in the art well-known golden standard of such a categorical classification. In DSM-IV, there is no assumption that each category of mental disorder is a completely discrete entity with absolute boundaries dividing it from other mental disorders or from no mental disorder. There is also no assumption that all individuals described as having the same mental disorder are alike in all important ways. Individuals sharing a diagnosis are likely to be heterogeneous even in regard to the defining features of the diagnosis. Thus, the categorical defined mental disorders as mood and anxiety disorders are having an external and even internal variable co-incidence of symptoms concerning e.g. mood, anxiety, perception, feeding, somatic sensations, sexual functions, sleep, cognitive functioning, impulse control, attention, substance use, personality, bereavement, identity, phase of life, abuse or neglect and other aspects of behavior.
In a dimensional system, clinical presentations are classified based on quantification of attributes i.e. dysfunctions rather than the assignment to categories and works best in describing phenomena that are distributed continuously and that do not have clear boundaries.
Emotion dysregulation is known as such an attribution or dysfunction that plays an important role in the development and course of mental disorders (Gross, J. J. & Munoz. R. F., 1995, Emotion regulation and mental health, Clinical Psychology: Science and Practice, 2, 151-164; Mennin, D. S., Heimberg, R. G., Turk, C. L. & Fresco, D. M., 2002, Applying an emotion regulation framework to integrative approaches to generalized anxiety disorder, Clinical Psychology: Science and Practice, 9, 85-90; Linehan, M. M., 1993, Cognitive-behavioral treatment of borderline personality disorder, New York, The Guilford Press; Gratz, K. L., Roemer, L., 2001 & 2004, Multidimensional assessment of emotion regulation and dysregulation: development, factor structure, and initial validation of the Difficulties in Emotion Regulation Scale, Annual meeting of the Association for Advancement of Behavior Therapy, November 2001 & Journal of Psychopathology and Behavioral Assessment, Vol. 26, No. 1, March 2004) besides behavioural and cognitive dysfunctions. D4 dopamine receptors (D4DR), almost exclusively present in the mesocortical and mesolimbic systems (O'Malley, K. L., Harmon, S., Tang, L., Todd, R. D., The rat dopamine D4 receptor; sequence, gene structure, and demonstration of expression in the cardiovascular system, New Biol., 4, 137-46, 1992), are in the art known as modulators of emotion and cognition. D4DR agonistic activity gives a behavioural sensitisation; D4DR antagonistic activity leads to an emotion modulation (Svensson, T. H., Mathé, A. A., Monoaminergic Transmitter Systems, Biological Psychiatry (eds. D'Haenen, H., et al.), 45-66, 2002, John Wiley & Sons, Ltd). Data demonstrate that agonism of the dopamine D4 receptors play an important role in the induction of behavioral sensitization to amphetamine and accompanying adaptations in pre- and postsynaptic neural systems associated with the mesolimbocortical dopamine projections (D. L. Feldpausch et al.; The Journal of Pharmacology and Experimental Therapeutics Vol. 286, Issue 1, 497-508, July 1998).
Results suggest that the antagonisms of cortical D2 dopamine receptors are a common target of traditional and atypical antipsychotics for therapeutic action. Higher in vivo binding to the D2 receptors in the cortex than in the basal ganglia is suggested as an indicator of favorable profile for a putative antipsychotic compound (X. Xiberas and J. L. Martinot; The British Journal of Psychiatry (2001) 179: 503-508). Results show that dopamine D4 receptor antagonism in the brain does not result in the same neurochemical consequences (increased dopamine metabolism or hyperprolactinemia) observed with typical neuroleptics (Smite Patel at al., The Journal of Pharmacology and Experimental Therapeutics Vol. 283, Issue 2, 636-647, 1997). The selective D4 dopamine receptor antagonist L-745,870 was ineffective as an antipsychotic for the treatment of neuroleptic responsive patients with acute schizophrenia (Kramer, M. S. et al., Arch. Gen. Psychiatry 1997 December; 54(12):1080).
Finally, in the biological system, mental disorders are defined on other levels of abstraction than in the categorical and dimensional system. Structural pathology (e.g. amyloid plaques in Alzheimer Disease), etiology (e.g. HIV Dementia) and deviance from a physiological norm (e.g. reduced cerebral blood flow) are often used as indicative biological markers for a mental disorder. The underlying dysregulation of various neurotransmittor systems (glutaminergic, GABAergic, cholinergic, monoaminergic (nor-adrenergic, dopaminergic, serotonergic), etc.) is the in the art used model for the explanation of the biological determinants of the clinical presentation of mental disturbances. It is known that the Serotonin 2A Receptor (5-HT2A receptor)—which is widespread in the Central Nervous System (CNS)—has a regulating role on the dysregulation of various neuro-transmitter systems. 5-HT2A agonism gives several behavioural disturbances; 5-HT2A antagonism leads to a governance of mood, social behaviour, anxiety, cognitive function, stress, sleep functions, nociception, sexual functions, feeding and other aspects of behaviour (J. E. Leysen (2004) 5-HT2 Receptors; Current Drug Targets—CNS & Neurological Disorders, 2004, 3, 11-26).
Dysregulation of the HPA axis (hypothalamic-pituitary-adrenal axis) has frequently been reported in patients with psychiatric disorders, and is among the most robustly demonstrated neurobiological changes among psychiatric patients (D. A. Gutman and C. B. Nemeroff, Neuroendocrinology, Biological Psychiatry (eds. D'Haenen, H., et al), 99, 2002, John Wiley & Sons, Ltd). The resulting elevated plasma cortisol concentrations leads to an enhanced binding of serotonin for the 5-HT2A receptor (E. A. Young, Mineralocorticoid Receptor Function in Major Depression, Arch. Gen. Psychiatry, January 2003; 60: 24-28) and thus agonism.
Additionally 5-HT2A antagonism gives a des-inhibiting of the inhibitory effect of the 5-HT2A receptor on (i) the 5-HT1A receptor stimulation by serotonin (S. M. Stahl, Newer Antidepressants and Mood Stabilizers, Essential Psychopharmacology, 265, University Press; 2 edition (Jun. 15, 2000); ISBN: 0521646154) and on (ii) the dopamine release in the mesocortical systems (S. M. Stahl, Classical Antidepressants, Serotonin Selective and Noradrenargic Reuptake Inhibitors, Essential Psychopharmacology, 233, University Press; 2 edition (Jun. 15, 2000); ISBN: 0521646154).
Clinical or real effectiveness of psychopharma is very rare via common pooping-out; many treatment-refractory patients and up to half of patients fail to attain remission (S. M. Stahl, Essential Psychopharmacology, Depression and Bipolar Disorders, 151, University Press; 2 edition (Jun. 15, 2000); ISBN: 0521646154). Implications of not attaining remission for Mental Disorders are increased relapse rates, continuing functional impairment and increased suicide rate (S. M. Stahl, Essential Psychopharmacology, Depression and Bipolar Disorders, 152, University Press; 2 edition (Jun. 15, 2000); ISBN: 0521646154). Clinical causes of not attaining remission by the Current Psychopharmacological Compounds are inadequate early treatment, underlying emotion dysregulation (affecting instability-hypersensitivity-hyperaesthesia-dissociative phenomena, etc.) and competitive antagonism. There is thus a growing need for a more efficient therapy and more efficient, selective and efficacious medicaments for treating mental disorders.